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Chronic, Noninfectious Diarrhea: A Review

Author/s: 
Prashant Singh, Allen Lee, Neil M. Sheth

Importance: Chronic diarrhea is defined as loose or watery stools lasting longer than 4 weeks and affects approximately 6% to 7% of adults in the US. More than 90% of patients with chronic diarrhea have a noninfectious etiology.

Observations: The most common causes of chronic, noninfectious diarrhea are irritable bowel syndrome with diarrhea (IBS-D) and functional diarrhea. IBS-D typically presents with recurrent abdominal pain relieved or worsened after defecation. Functional diarrhea is a condition in which more than 25% of bowel movements in the preceding 3 months are loose or watery, but it is not associated with significant abdominal pain. Chronic diarrhea due to a small-bowel source, such as celiac disease or small intestinal bacterial overgrowth, is typically associated with large-volume diarrhea and weight loss, with or without steatorrhea. Celiac disease is an autoimmune condition defined by enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals, and small intestinal bacterial overgrowth is characterized by excessive bacteria in the small bowel. Chronic diarrhea due to colon pathology, such as bile acid diarrhea and microscopic colitis, typically presents with frequent, low-volume stools, with or without urgency and excess mucus. Bile acid diarrhea is characterized by excess bile acids in the colon, and microscopic colitis is characterized by chronic inflammation on colon biopsies despite normal endoscopic appearance. Evaluation of chronic diarrhea includes serological testing for celiac disease (tissue transglutaminase immunoglobulin A, along with total immunoglobulin A) and stool testing for fecal calprotectin to evaluate for inflammatory bowel disease. Patients with gastrointestinal bleeding, unexplained weight loss, 45 years or older, nocturnal diarrhea, steatorrhea, and/or iron deficiency anemia should undergo colonoscopy to evaluate for colorectal cancer as well as upper endoscopy. During colonoscopy, random biopsies are recommended to evaluate for microscopic colitis, which affects 13% of patients with chronic diarrhea. If evaluation does not identify a cause of chronic diarrhea, likely diagnoses are IBS-D or functional diarrhea and the patient should be treated with lifestyle modification, such as regularly scheduled meals, exercise, intake of at least 8 cups of noncaffeinated fluids daily, limiting caffeine to 3 cups or fewer daily, and avoiding alcohol and carbonated beverages. For general treatment of chronic diarrhea, dietary modifications, such as consuming a diet low in fermentable oligosaccharides (legumes, wheat, onions, garlic), disaccharides (lactose), and monosaccharides (fructose), and polyols (sorbitol, mannitol), or medications, such as opiate agonists (loperamide), anticholinergics (hyoscyamine, dicyclomine), or 5-hydroxytryptamine 3 receptor (5-HT3) antagonists (ondansetron), can be prescribed. These therapies typically improve diarrhea in 50% to 80% of patients.

Conclusions and relevance: The most common causes of chronic, noninfectious diarrhea include IBS-D and functional diarrhea. Diagnostic testing should include consideration of celiac disease, inflammatory bowel disease, and microscopic colitis. Empiric therapies for chronic diarrhea include lifestyle and dietary modifications and medications, including opiate agonists, anticholinergics, and 5-HT3 antagonists.

Keywords 
Diarrhea infectious diarrhea Irritable Bowel Syndrome abdominal pain Defecation Steatorrhea

Gastric Cancer: A Review

Author/s: 
Anuj Kishor Patel, Nilay S. Sethi

Importance Globally, 968 350 new cases and 659 853 deaths from gastric cancer were reported in 2022. In the US, 30 300 new cases and 10 780 deaths were estimated in 2025.

Observations Gastric cancer is more common in men, and the median age at diagnosis is 68 years. Most gastric cancers (>90%) are adenocarcinomas. Worldwide, 85% of cases arise from the stomach body or antrum and 15% from the cardia. In the US, more than 90% of patients diagnosed with gastric cancer present with symptoms such as weight loss and abdominal pain. At presentation, approximately 13% have localized disease (limited to the stomach), 15% to 25% have locally advanced disease, defined as a tumor that has spread to regional lymph nodes, and 35% to 65% have metastatic disease. Helicobacter pylori infection is a treatable risk factor associated with 90% of gastric body and antrum cancers globally. Additional modifiable risk factors include smoking, alcohol, obesity, and salt intake. In countries with high incidence such as Japan and Korea, routine endoscopic screening beginning at age 40 years is associated with improved survival. Diagnosis is made by endoscopic biopsy. Patients with localized gastric cancer are treated with surgical resection and have a 5-year relative survival rate of 75% with treatment. Patients with more advanced-stage disease should receive gastrectomy, perioperative chemotherapy with 5-fluorouracil, oxaliplatin, and docetaxel and immunotherapy (durvalumab). Metastatic or unresectable disease may be treated with chemotherapy, immunotherapy, and/or targeted therapy depending on biomarkers, including programmed cell death ligand 1 (PD-L1), human epidermal growth factor receptor 2 (ERBB2; formerly HER2 or HER2/neu), and claudin-18, isoform 2 (CLDN18.2). For PD-L1–expressing gastric cancer, adding immune checkpoint inhibitors, such as nivolumab and pembrolizumab, is associated with an additional 3 months of survival when compared with chemotherapy alone. For gastric cancers overexpressing the ERBB2 or CLDN18.2 proteins, the addition of trastuzumab or zolbetuximab, respectively, is associated with an additional 3 to 4 months’ survival. Early supportive care focusing on symptom management and on nutritional and psychosocial support is associated with 3 months of survival benefit. Less than 10% of patients with metastatic gastric cancer survive more than 5 years.

Conclusions and Relevance Approximately 30 300 new cases of gastric cancer are diagnosed annually in the US. Localized gastric cancer is treated with gastrectomy, and locally advanced disease is treated with surgery and chemoimmunotherapy. For patients with unresectable or metastatic gastric cancer, chemotherapy with immune checkpoint inhibitors and targeted therapies such as trastuzumab or zolbetuximab improves survival by several months.

Keywords 
oncology Gastroenterology Stomach Neoplasms adenocarcinoma Helicobacter Infections abdominal pain

Diagnosis and management of celiac disease

Author/s: 
Jedid-Jah Blom, Dominica Gidrewicz, Justine Turner, Donald R. Duerksen, M. Ines Pinto-Sánchez

Celiac disease is frequently undiagnosed, in part because of its highly variable clinical presentation.

Celiac disease can present with classic gastrointestinal symptoms (e.g., diarrhea, abdominal pain, bloating, weight loss), atypical or extraintestinal manifestations (e.g., anemia, osteoporosis, neurologic symptoms, infertility, fatigue) or asymptomatic presentations detected from screening.

The first-line serologic screening test measures tissue transglutaminase immunoglobulin A and should be conducted while the patient is consuming gluten.

Complications of celiac disease include nutritional deficiencies, osteoporosis, increased risk of viral infections and pneumonia, and, rarely, risk of malignancy.

Adherence to a lifelong, strict gluten-free diet with regular monitoring of disease activity and nutritional status is key for symptom management and to prevent complications.

Keywords 
celiac disease diet Gluten-Free

Acute Abdomen in the Modern Era

Author/s: 
Selwyn O Rogers Jr, Orlando C Kirton

Acute abdominal pain is one of the most common symptoms in patients presenting to the emergency department and accounts for 5 to 10% of all emergency department visits. Pathophysiological conditions that lead to surgical interventions in such patients are mainly gastrointestinal obstruction, hemorrhage, ischemia, and viscus perforation. Acute abdominal pain can be diffuse or localized (i.e., quadrant-based epigastric pain or pain in the right upper quadrant, left upper quadrant, right lower quadrant, or left lower quadrant)2,4,6 and is associated with but not limited to the following disease processes: perforated viscus, peptic ulcer disease, mesenteric ischemia, acute cholecystitis, appendicitis, diverticulitis, pancreatitis, and intraabdominal hemorrhage. The need for emergency general surgery is an independent risk factor for postoperative complications and death, indicating the severity of the condition. Therefore, timely diagnosis of acute abdominal emergencies is essential. From antiquity to modern times, medical students have been taught that the history and the physical examination are the central components in the evaluation of acute abdominal pain.

Keywords 
Abdomen acute abdomen diagnosis abdominal pain

Incidence, co-occurrence, and evolution of long-COVID features: A 6-month retrospective cohort study of 273,618 survivors of COVID-19

Author/s: 
Taquet, M., Dercon, Q., Luciano, S., Geddes, J. R., Husain, M., Harrison, P. J.

Background
Long-COVID refers to a variety of symptoms affecting different organs reported by people following Coronavirus Disease 2019 (COVID-19) infection. To date, there have been no robust estimates of the incidence and co-occurrence of long-COVID features, their relationship to age, sex, or severity of infection, and the extent to which they are specific to COVID-19. The aim of this study is to address these issues.

Methods and findings
We conducted a retrospective cohort study based on linked electronic health records (EHRs) data from 81 million patients including 273,618 COVID-19 survivors. The incidence and co-occurrence within 6 months and in the 3 to 6 months after COVID-19 diagnosis were calculated for 9 core features of long-COVID (breathing difficulties/breathlessness, fatigue/malaise, chest/throat pain, headache, abdominal symptoms, myalgia, other pain, cognitive symptoms, and anxiety/depression). Their co-occurrence network was also analyzed. Comparison with a propensity score–matched cohort of patients diagnosed with influenza during the same time period was achieved using Kaplan–Meier analysis and the Cox proportional hazard model. The incidence of atopic dermatitis was used as a negative control.

Among COVID-19 survivors (mean [SD] age: 46.3 [19.8], 55.6% female), 57.00% had one or more long-COVID feature recorded during the whole 6-month period (i.e., including the acute phase), and 36.55% between 3 and 6 months. The incidence of each feature was: abnormal breathing (18.71% in the 1- to 180-day period; 7.94% in the 90- to180-day period), fatigue/malaise (12.82%; 5.87%), chest/throat pain (12.60%; 5.71%), headache (8.67%; 4.63%), other pain (11.60%; 7.19%), abdominal symptoms (15.58%; 8.29%), myalgia (3.24%; 1.54%), cognitive symptoms (7.88%; 3.95%), and anxiety/depression (22.82%; 15.49%). All 9 features were more frequently reported after COVID-19 than after influenza (with an overall excess incidence of 16.60% and hazard ratios between 1.44 and 2.04, all p < 0.001), co-occurred more commonly, and formed a more interconnected network. Significant differences in incidence and co-occurrence were associated with sex, age, and illness severity. Besides the limitations inherent to EHR data, limitations of this study include that (i) the findings do not generalize to patients who have had COVID-19 but were not diagnosed, nor to patients who do not seek or receive medical attention when experiencing symptoms of long-COVID; (ii) the findings say nothing about the persistence of the clinical features; and (iii) the difference between cohorts might be affected by one cohort seeking or receiving more medical attention for their symptoms.

Conclusions
Long-COVID clinical features occurred and co-occurred frequently and showed some specificity to COVID-19, though they were also observed after influenza. Different long-COVID clinical profiles were observed based on demographics and illness severity.

Author summary
Why was this study done?
Long-COVID has been described in recent studies. But we do not know the risk of developing features of this condition and how it is affected by factors such as age, sex, or severity of infection.
We do not know if the risk of having features of long-COVID is more likely after Coronavirus Disease 2019 (COVID-19) than after influenza.
We do not know about the extent to which different features of long-COVID co-occur.
What did the researchers do and find?
This research used data from electronic health records of 273,618 patients diagnosed with COVID-19 and estimated the risk of having long-COVID features in the 6 months after a diagnosis of COVID-19. It compared the risk of long-COVID features in different groups within the population and also compared the risk to that after influenza.
The research found that over 1 in 3 patients had one or more features of long-COVID recorded between 3 and 6 months after a diagnosis of COVID-19. This was significantly higher than after influenza.
For 2 in 5 of the patients who had long-COVID features in the 3- to 6-month period, they had no record of any such feature in the previous 3 months.
The risk of long-COVID features was higher in patients who had more severe COVID-19 illness, and slightly higher among females and young adults. White and non-white patients were equally affected.
What do these findings mean?
Knowing the risk of long-COVID features helps in planning the relevant healthcare service provision.
The fact that the risk is higher after COVID-19 than after influenza suggests that their origin might, in part, directly involve infection with SARS-CoV-2 and is not just a general consequence of viral infection. This might help in developing effective treatments against long-COVID.
The findings in the subgroups, and the fact that the majority of patients who have features of long-COVID in the 3- to 6-month period already had symptoms in the first 3 months, may help in identifying those at greatest risk.

Managing nonspecific abdominal pain in children and young people

Author/s: 
Chanchlani, Neil, Walters, Thomas D., Russell, Richard K.

KEY POINTS

• Children present frequently to primary and emergency care with nonspecific abdominal pain.

• Only a few treatment options exist to manage colicky, undifferentiated pain; however, most children will not present more than once or twice to health services for this problem.

• Undifferentiated abdominal pain is poorly understood but likely multifactorial, arising from a combination of sensitizing medical events, psychosocial events and visceral hyperalgesia.

• Among children who seek health care for this problem, 20%–25% go on to be diagnosed with a disorder of the brain–gut axis, “a functional gastrointestinal disorder,” for which international guidelines exist to guide management.

• At first consultation, it is important to establish a positive therapeutic relationship between the clinician and the child and their parents, focusing on optimizing symptom control over unnecessary investigation and medicines.

Keywords 
children Emergency Care

The 2020 Medicare Documentation, Coding, and Payment Update

Author/s: 
Moore, K., Mullins, A., Solis, E.

As usual, the new year brings changes in how doctors bill and get paid for the services they provide to Medicare patients. The reforms that will most affect family physicians’ pay aren’t coming until 2021, when several changes in evaluation and management (E/M) coding and payment are projected to result in a 12% increase for family medicine.1 But there are still a host of things family physicians should know for 2020, including new codes to help you get paid for interacting with patients via the internet and new codes that should help make chronic care management (CCM) more financially rewarding. The Centers for Medicare & Medicaid Services (CMS) is also continuing its quest to streamline documentation requirements and develop new payment models intended to reward quality instead of volume. This article summarizes the 2020 changes most relevant to family medicine. As always, private payers’ policies may differ, so consult with your billing staff to understand any important differences.

Keywords 
coding
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